4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-1H-indole synthesis

Yield:1622173-47-0 63%

Reaction Conditions:

with dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂;potassium acetate in 1,4-dioxane at 100; for 2 h;Inert atmosphere;Sealed tube;

Steps:

37 Intermediate 374-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-2,3-dihydro-1 H-indole

A solution of 4-bromoindoline (694 mg, 3.50 mmol, 1.0 eq) in 1,4-dioxane (10 mL) was degassed with argon for 30 mm before the addition of bis(pinacolato)diboron (1 .07 g, 4.20 mmol, 1 .2 eq). Whilst degassing, potassiumacetate (1.03 g, 10.5 mmol, 3.0 eq) and PdCI2(dppf)CH2CI2 (143 mg, 0.175mmol, 5 mol%) were added. The vessel was then sealed and stirred at 100°C for2 h. Upon cooling, the reaction mixture was diluted with H20 (5 mL), poured into50% brine (15 mL) and extracted with EtOAc (3 x 20 mL). The combined organicextracts were dried over MgSO4, filtered and concentrated in vacuo. Purificationby silica gel column chromatography with hexane/EtOAc (1:0-9:1) yieldedIntermediate 37 as a cream solid (539 mg, 63%).1H NMR (300MHz, CDCI3) oH. 7.17 (d, J=7.5 Hz, 1H), 7.04 (t, J7.5 Hz, 1H),6.77 (d, J=7.5 Hz, 1H), 3.48-3.61 (m, 2H), 3.18-3.31 (m, 2H), 1.84 (br. 5., 1H),1.33 (5, 12H).MS (ESj 246.2 (100%, [M+H]j.

References:

WO2017/29521,2017,A1 Location in patent:Page/Page column 48; 49